Human Immunology News Volume 5.30 | Aug 1 2017

TOP STORY

Novel In Vitro Booster Vaccination to Rapidly Generate Antigen-Specific Human Monoclonal Antibodies

Scientists introduced an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induced antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. [J Exp Med] Full Article

(Ranked by impact factor of the journal)

Multifaceted Role of BTLA in the Control of CD8⁺ T Cell Fate after Antigen Encounter

Investigators determined the functional role and downstream signal of B-and-T lymphocyte attenuator (BTLA) in both human CD8⁺ tumor-infiltrating lymphocytes (TILs) and mouse CD8⁺ T cells. CD8⁺BTLA^– TILs could not control tumor growth in vivo as well as their BTLA⁺ counterpart and antigen-specific CD8⁺BTLA^– T cells had impaired recall response to a vaccine. [Clin Cancer Res] Abstract

Identification of a Novel Population of Highly Cytotoxic c-Met-Expressing CD8⁺ T Lymphocytes

The authors showed that a fraction of murine effector CD8⁺ cytotoxic T lymphocytes (CTLs) expressed the hepatocyte growth factor receptor c-Met (c-Met⁺ CTLs). Phenotypic and functional analysis of c-Met⁺ CTLs revealed that they display enhanced cytolytic capacities compared to their c‐Met⁻ CTL counterparts. [EMBO Rep] Abstract | Graphical Abstract

Hobit Expression by a Subset of Human Liver-Resident CD56^bright Natural Killer Cells

Scientists assessed the expression and contribution of Hobit to tissue-residency of natural killer (NK) cells in the human liver. They showed that the transcription factor Hobit identified a subset of NK cells in human livers that expressed a distinct set of adhesion molecules and chemokine receptors consistent with tissue residency. [Sci Rep] Full Article

The Maintenance of Telomere Length in CD28⁺ T Cells during T Lymphocyte Stimulation

Investigators found that telomerase activation was not required for the short-term proliferation of T cells and that telomeres progressively shortened in a heterogeneous population of T cells, even if telomerase was detected. [Sci Rep] Full Article

IL-33-Expanded Human Vγ9Vδ2 T Cells Have Anti-Lymphoma Effect in a Mouse Tumor Model

Researchers showed that human Vγ9 T cells were able to proliferate in a mouse model with the combination of phosphoantigen and rhIL-33, and that IL-33-expanded Vγ9 T cells could prevent tumor growth in a mouse lymphoma model. [Eur J Immunol] Abstract

Targeting Interferon-Alpha to Dendritic Cells Enhances a CD8⁺ T Cell Response to a Human CD40-Targeted Cancer Vaccine

Contrary to in vitro-derived monocyte dendritic cells (DCs), scientists found that interferon-alpha (IFNα) stimulation of human blood-derived DCs was necessary for an antigen-specific IFNγ CD8⁺ T cell response to a CD40 targeted cancer vaccine. [Vaccine] Abstract

miR-181d Regulates Human Dendritic Cell Maturation through NF-κB Pathway

The authors investigated the functions of miR-181d in dendritic cell maturation, and explored the underlying mechanisms. They showed that miR-181d activated the NF-κB pathway and also promoted the expression of pro-inflammatory cytokine IL12 and TNF-α. [Cell Prolif] Abstract

Analysis of the CD8⁺ T Cell Anti-HIV Activity in Heterologous Cell Co-Cultures Reveals the Benefit of Multiple HLA Class I Matches

To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, scientists co-cultured primary CD8⁺ T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4⁺ T cells. [Immunogenetics] Abstract

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Tonic Signals: Why Do Lymphocytes Bother?

Researchers summarize what is known about the mechanistic and functional details of tonic signaling. They highlight recent advances that have increased the understanding of how the amount of tonic signal impacts immune function, describing novel tools that have moved the field forward and toward a molecular understanding of tonic signaling. [Trends Immunol] Abstract

Development of Autoantibodies Precedes Clinical Manifestations of Autoimmune Diseases: A Comprehensive Review

The role of autoantibodies in the pathogenesis of autoimmune diseases, whether they actually affect disease progression or are merely an epiphenomenon is still not completely clear in many autoimmune diseases. Because of the gaps in knowledge, the ability to accurately predict a future autoimmune disease can only be considered a relative risk factor. [J Autoimmun] Abstract

Acid Sphingomyelinase Mediates Human CD4⁺ T-Cell Signaling: Potential Roles in T-Cell Responses and Diseases

Investigators summarize the pivotal roles of acid sphingomyelinase in the regulation of human CD4⁺ T-cell activation and responses. [Cell Death Dis] Full Article

B Cells and Their Cytokine Activities Implications in Human Diseases

B cells are the only cell type that can give rise to antibody-producing cells, and the only cell type whose selective depletion can, today, lead to an improvement of a wide range of immune-mediated inflammatory diseases, including disorders not primarily driven by autoantibodies. The author discusses this paradoxical observation, and proposes that the capacity of B cells to act as cytokine-producing cells explains how they can control monocyte activity and subsequently disease pathogenesis. [Clin Immunol] Full Article

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Atara Biotherapeutics Announces Two Presentations, Including Updated, Interim Results from a Phase I Study of Autologous ATA188 in Patients with Progressive Multiple Sclerosis (MS)

Atara Biotherapeutics, Inc. announced that the company’s collaborating investigators will present results from two studies. [Press release from Atara Biotherapeutics, Inc. discussing research to be presented at the MSParis 2017 Congress, Paris] Press Release

New Stand Up To Cancer-Lustgarten Foundation Research Team Aims to Apply CAR T-Cell Therapy to Pancreatic Cancer

Stand Up To Cancer (SU2C) is supporting a new translational research team to explore how a type of immunotherapy that has been very successful in blood cancers can be applied to pan​creatic cancer, the American Association for Cancer Research, SU2C’s Scientific Partner, announced. [American Association for Cancer Research] Press Release

Protalex Completes Data Analysis of Second Dose Cohort of U.S. Phase I/II Study of PRTX-100 in ITP

Protalex, Inc. announced that following completion of a planned interim analysis of safety and efficacy data from the second dose cohort, the company is escalating the dose of PRTX-100 in its U.S. Phase I/II study of PRTX-100 in adults with persistent/chronic immune thrombocytopenia (ITP). [Protalex, Inc.] Press Release

Seattle Children’s Opens CD22 CAR T-Cell Immunotherapy Trial for Children and Young Adults Whose Leukemia Escapes CD19 CAR T-Cell Therapy

Researchers have opened a Phase I clinical trial, PLAT-04, for children and young adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia. They will examine the safety, feasibility and efficacy of administering cancer-fighting chimeric antigen receptor (CAR) T cells that have been reprogrammed to target the CD22 protein expressed by some leukemia cells. [Seattle Children’s Hospital] Press Release

Kymab’s KY1005 Antibody in Clinical Trial

Kymab announced that KY1005, its novel human antibody therapeutic, has successfully completed dosing of the 24^th subject in its first clinical study. [Kymab] Press Release

Cesca Therapeutics Announces Issuance of New Cellular Processing Patent Poised to Revolutionize CAR-T Cell Manufacturing

Cesca Therapeutics Inc. announced that the U.S. Patent and Trademark Office has awarded a new U.S. Patent entitled “Cell Separation Devices, Systems, and Methods.” The patent relates to the automated isolation of rare, therapeutically critical target cells from blood, bone marrow, leukapheresis product, and other cell sources, while maintaining the viability of the cells under asceptic conditions. [Cesca Therapeutics Inc.] Press Release

University of Tokyo Probe Says Chromosome Team Doctored Images

After a nearly year-long investigation into anonymous allegations of data and image falsification in numerous papers, a University of Tokyo committee announced it had confirmed that one research group falsified images and graphs in five papers. The panel cleared five other research groups of wrongdoing. [ScienceInsider] Editorial

Why Would a University Pay a Scientist Found Guilty of Misconduct to Leave?

In June 2016, investigators at the University of Georgia in Athens concluded that Azza El-Remessy, a faculty member who studied the impact of diabetes on the eye, had committed misconduct and recommended she be terminated. El-Remessy hired a lawyer to dispute the findings, but the following October she gave up her challenge after the university paid her $100,000—essentially to leave. [ScienceInsider] Editorial

China Cracks Down after Investigation Finds Massive Peer-Review Fraud

A massive peer-review fraud has triggered a tough response from the Chinese government. Officials announced that more than 400 researchers listed as authors on some 100 now-retracted papers will face disciplinary action because their misconduct has seriously damaged China’s scientific reputation. [ScienceInsider] Editorial

At Harvard, Extraordinary Court Battle between Ph.D. Student and Prominent Researcher Grinds On

The conflict between Gustavo German, a Harvard doctoral student in biomedicine, and Lee Rubin, a prominent stem cell researcher, has continued to evolve. Amid continued legal jousting, the situation has remained difficult for all of the parties involved in this tumultuous episode. [ScienceInsider] Editorial

NEW Multiple Sclerosis: Conventional and Alternative Therapeutic Approaches
August 15, 2017
Online

NEW Keystone Symposia: T Cell Dysfunction, Cancer and Infection
January 16-20, 2018
Breckenridge, Colorado, United States

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NEW Postdoctoral Researcher – Inflammatory Diseases (University of Pennsylvania)

NEW Assistant Professor – Cell Science (University of Manitoba)

Postdoctoral Research Associate – Autoimmune Disease Research (Benaroya Research Institute at Virginia Mason)

Postdoctoral Fellow – B Cells in Autoimmune Diseases (Inserm)

Postdoctoral Fellow – Inflammatory Autoimmune Disease (Vanderbilt University Medical Center)

Postdoctoral Position – Molecular Biology and Immunology (Harvard Medical School)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Postdoctoral Research Fellow – Innate Immunity (Fred Hutchinson Cancer Research Center)

Assistant, Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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